Prader-Willi syndrome (PWS) is a genetic disorder that occurs in approximately one out of every 16,000 births. This rare complex and multisystem genetic disorder is caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13 that may occur via one of three main mechanisms: paternal microdeletion, maternal uniparental disomy, and imprinting defect.
The course and natural history of PWS has classically been described as consisting of two distinct clinical stages, albeit current knowledge indicates these are more nuanced than originally thought. The first stage occurs during the neonatal and early infancy period, and is characterized by varying degrees of hypotonia, weak cry, poor suck reflex, feeding difficulties (failure to thrive), developmental delay, temperature instability, and underdeveloped sex organs (hypogonadism). Motor and language development delays are also notable during this first stage. The neonatal symptoms typically improve by 9-25 months of age, along with improved muscle tone, the child becomes more alert, and with more appropriate appetite.
The second stage of PWS (beginning ˜2-4 years of age) is characterized by more rapid weight gain, onset and escalation of hyperphagia, and continued growth and developmental delays. In addition, as hyperphagia emerges, a separate and distinctly negative constellation of maladaptive or problematic behaviors is observed. These maladaptive (problematic) behaviors include temper tantrums, irritability, stubbornness, repetitive and compulsive behaviors, and aggression. External food limits and supervision are needed. Otherwise, individuals with PWS face the risk of life-threatening obesity. Once food-seeking behavior ensues, parents will generally implement food security, reduced caloric intake, and constant supervision at meals and around food access. Even with supervision, many persons with PWS are quite adept and clever in obtaining food. Obesity as a life-threatening condition and the concurrent, and often time severe maladaptive behavioral difficulties, are the central challenging issues for individuals with the syndrome and their families.